Mendelian randomization analysis does not reveal a causal association between genetic liability to chronic pain and...

Although observational studies suggest potential comorbidities between chronic pain (CP) and autism spectrum disorder (ASD), causal relationship remains unclear. This study aimed to investigate the causal association between genetic liability to CP and ASD using a bidirectional Mendelian Randomization (MR) analysis.

Genome-wide association summary-level data for CP and ASD were sourced from public databases. Single nucleotide polymorphisms (SNPs) were used as instrumental variables (IVs) in MR analysis. Inverse variance weighted (IVW) was the primary MR method, with MR-Egger, weighted median, and maximum likelihood analyses supplementing IVW results. Forward MR analysis evaluated the causal effect of CP on ASD, and reverse MR analysis assessed the causal impact of ASD on CP. Various sensitivity tests were performed for MR results' reliability.

The forward MR analysis found no causal effect of seven CP types on ASD (P > 0.05). Similarly, reverse MR analysis showed no causal effect of ASD on seven CP types (P > 0.05). Sensitivity tests confirmed results' reliability: (i) Cochran's Q test showed no significant heterogeneity; (ii) MR-Egger intercept test and MR-PRESSO global test indicated no horizontal pleiotropy; (iii) leave-one-out test confirmed the stability of the MR results.

This bidirectional MR analysis did not find evidence for a causal relationship between genetic liability to CP and ASD. The observed comorbidity may be due to shared mechanisms rather than direct causation. Further research is needed to explore these mechanisms and inform therapeutic strategies.